Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neural regulation of islets of Langerhans mediates responses to stress and food ingestion. Transplantation of isolated islets offers hope to patients with insulin dependent diabetes mellitus but denervation of isolated islets may affect the capacity for appropriate metabolic control. Previous examination of the endocrine response to stress in islet autografted dogs revealed differences consistent with loss of neural regulation. Therefore, in the present study, islets grafted in rats were examined for extent and nature of reinnervation. Islets isolated from syngeneic donors were grafted under the kidney capsule of Wistar-Furth rats (n = 7) after 3 wk of streptozotocin induced diabetes. After 4 mo, graft-bearing kidneys were recovered and processed for double immunofluorescence. Antibodies were directed against (a) neuron associated proteins: synapsin (SYN) and L1; (b) neurotransmitters; tyrosine hydroxylase (TH), neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and calcitonin gene-related peptide (CGRP); and (c) islet hormones: insulin and somatostatin. SYN and L1 immunoreactivities in nerve fibres suggested reinnervation of the grafted islets although fibres were not associated with structures within the transplanted islets as in intact islets. CGRP immunoreactivity was observed in fibres and in a subpopulation of cells within intact islets but only in cells of the grafted islets. VIP, TH, and NPY immunoreactivities were found in nerve fibres of intact islets but only VIP was observed in fibres of grafted islets suggesting an absence of sympathetic reinnervation. In conclusion, transplanted islets of Langerhans become reinnervated but with a distribution and complement of neurotransmitters distinct from intact islets.
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PMID:Reinnervation of isolated islets of Langerhans transplanted beneath the kidney capsule in the rat. 791 58

Glucagon-like peptide-1 (GLP-1) is promptly released from endocrine cells of the distal part of the gut after oral ingestion of a meal. To test the possibility that hormones produced by the proximal small intestine or transmitters of the enteric nervous system may be involved in the early phase of meal-induced GLP-1 secretion, various intestinal regulatory peptides and neurotransmitters of the gut were administered intraarterially in the isolated vascularly perfused rat colon preparation. The release of GLP-1 in the portal effluent was measured by a specific RIA. Intraarterial infusion of glucose-dependent insulinotropic peptide (GIP) over the concentration range 0.25-1 nM evoked a dose-dependent release of GLP-1, with a maximal response of 350% of the basal value. Tetrodotoxin did not modify the GIP-induced release of GLP-1. Secretin or cholecystokinin did not stimulate the secretion of GLP-1. Bombesin (10(-9)-10(-7) M) provoked a dose-dependent release of GLP-1, consisting of an early peak, followed by a sustained response. Calcitonin gene-related peptide (5 x 10(-8) M) induced a dramatic rise of GLP-1 immunoreactivity in the portal effluent (peak at 800% of the basal value 10 min after the start of infusion). Similarly, the beta-adrenergic agonist isoproterenol at concentrations of 10(-7) and 10(-6) M provoked a pronounced release of GLP-1 (peak at 500% of the basal value with 10(-6) M isoproterenol). Finally, the muscarinic cholinergic agonist bethanechol at a concentration of 10(-4) M evoked a gradual increase in GLP-1 immunoreactivity, which reached a maximal value (900% over basal) at the end of the 30-min infusion period. The lowest concentration of bethanechol used in the present study (10(-5) M) did not increase portal GLP-1 immunoreactivity over the basal value. Tetrodotoxin did not modify the bethanechol-, isoproterenol-, calcitonin gene-related peptide-, or bombesin-induced GLP-1 release. In conclusion, the present study conducted with the isolated vascularly perfused rat colon shows that there are interactions between the two most potent incretins, GIP and GLP-1, probably through an enteroendocrine pathway. Additionally, several transmitters of the gut are potent stimulants of GLP-1 release and, therefore, represent potential tools in the treatment of the noninsulin-dependent diabetes mellitus.
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PMID:Regulation of glucagon-like peptide-1-(7-36) amide secretion by intestinal neurotransmitters and hormones in the isolated vascularly perfused rat colon. 798 23

A case of a 36-year patient with persistent diabetes mellitus of type I and gangrene of the foot is presented. Calcitonin has been used to treat osteitis and inflammation of the adjacent soft tissues. Despite performed surgery and conservative treatment, destruction of the bones has been progressing, and could lead to the high amputation of the extremity. Calcitonin produced an increase in bone, massive calcification around bone stumps, and anastomosis within one year. An acceleration of the wound healing has also been noted. Taking calcitonin mechanism of action and the clinical course of this case into consideration, it seems justified to use calcitonin in the treatment of gangrene of the foot in diabetes.
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PMID:[Calcitonin in treatment of diabetic foot syndrome]. 800 72

This study investigated whether alterations in bone mineral content (BMC) and/or in the phosphate-calcium metabolism exist in non-insulin-dependent diabetes mellitus (NIDDM); whether they are linked to glycaemic control and whether antidiabetic therapy--oral agents or insulin--influences BMC and mineral metabolism. A cross-section assessment compared BMC and mineral metabolism in 60 well-controlled and 50 poorly controlled diabetic patients under oral hypoglycaemic therapy with 50 healthy controls. A longitudinal assessment improved the high glucose levels of the poorly controlled diabetic group either by increasing oral treatment or by adding a bedtime NPH insulin. Glycaemic control, BMC and mineral metabolism were followed-up for 1 year. In NIDDM patients BMC is reduced. This reduction is more marked in poorly controlled diabetic patients. In well-controlled diabetes osteocalcin levels are low. In poorly controlled patients glycosuria, hypercalcuria and parathyroid hyperactivity are present. In both groups vitamins 25(OH)-D, 1,25(OH)2-D and calcitonin levels are normal. Improving metabolic control increased BMC, normalized urinary calcium excretion and parathyroid activity and reduced osteocalcin levels. The type of anti-diabetic therapy does not have any significant effect upon BMC or upon phosphate-calcium metabolism. In conclusion, in NIDDM a hard-to-define osteoblast deficit appears to exist. In poorly controlled diabetes the loss of BMC is aggravated by the negative calcium balance caused by the renal calcium leak. This is due to glucosuric-induced osmotic diuresis and is maintained by parathyroid activation.
Diabetes Res Clin Pract 1994 Feb
PMID:Osteopenia associated with non-insulin-dependent diabetes mellitus: what are the causes? 801 62

Neuropeptides are ubiquitous in the sympathetic system and modulate transmission at the levels of the intermediolateral cell column, sympathetic ganglia, and neuroeffector junctions. Several neuropeptide-containing pathways from the hypothalamus and medulla modulate excitability of preganglionic neurons. Neuropeptides coexist with norepinephrine or acetylcholine in subpopulations of chemically coded, target-specific sympathetic ganglion neurons. Neuropeptide Y is colocalized in adrenergic vasoconstrictor neurons, whereas vasoactive intestinal polypeptide is colocalized in cholinergic sudomotor neurons. Neuropeptide expression is plastic; during development, neurons that switch from a noradrenergic to a cholinergic phenotype increase expression of vasoactive intestinal polypeptide, somatostatin, and substance P. Preganglionic inputs increase neuropeptide Y and inhibit substance P expression. Sympathetic denervation produces sprouting of sensory fibers containing substance P and calcitonin gene-related peptide in target tissues. Neuropeptides from preganglionic fibers (e.g., enkephalin) and primary afferents (e.g., substance P, vasoactive intestinal polypeptide) modulate transmission in sympathetic ganglia. Neuropeptide Y produces vasoconstriction, prejunctional inhibition of norepinephrine release, and postjunctional potentiation of norepinephrine effects. Plasma neuropeptide Y increases during intense sympathoexcitation, hypertension, and pheochromocytoma. Dystrophic neurites containing neuropeptide Y occur in human sympathetic ganglia during aging, diabetes, and dysautonomia. Sympathetic neuropeptides may thus have important clinical implications.
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PMID:Neuropeptides in the sympathetic system: presence, plasticity, modulation, and implications. 802 63

To explore the pathogenesis of diabetes associated osteopenia, we characterized the osteopenia in streptozotocin (STZ)-diabetic rats pharmacologically and biochemically. The femur metaphyseal bone mineral density measured by single photon absorptiometry decreased time-dependently in the STZ rats compared with that in control, and the difference reached statistical significance from 2 weeks after treatment with STZ. Closely similar bone loss was obtained in ovariectomized (Ovx) and vitamin D deficient(D(-)) rats. Daily oral treatment with a bone resorption inhibitor, FR78844 (a bisphosphonate compound, 100 mg/kg), for 4 weeks significantly attenuated the osteopenia in the STZ and Ovx rats, but not in the D(-) rats, while 1 alpha-hydroxyvitamin D3 (1 alpha-(OH)D3) significantly attenuated the osteopenia in the STZ and D(-) rats in a dose of 0.1 microgram/kg/day, and that in the Ovx rats in 1 microgram/kg/day. The latter dose of 1 alpha-(OH)D3 significantly increased the metaphyseal bone mineral density of the femur in normal rats. Serum levels of 1 alpha, 25-dihydroxyvitamin D (1 alpha, 25-(OH)2D), the most active metabolite of vitamin D, hardly changed in the Ovx rats compared with that in control, but decreased to 24 and 76% that of control in the STZ and D(-) rats, respectively. Serum PTH levels in the STZ, Ovx and D(-) rats were comparable with those in controls, but serum calcitonin levels were reduced to 60 and 66% of control in the STZ and Ovx rats, respectively. Serum osteocalcin levels also decreased in the STZ rats compared to control. It is thus speculated that the predominance of bone resorption over bone formation and the reduction of 1 alpha, 25-(OH)2D are involved in the pathogenesis of diabetes associated osteopenia.
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PMID:Possible involvement of vitamin D3-deficiency and relatively enhanced bone resorption in the development of bone loss in streptozotocin-induced diabetic rats. 802 47

Recent studies have revealed that altered mineral and vitamin D metabolism is observed in diabetic patients with the complication of osteopenia. In order to elucidate the role of parathyroid hormone-related peptide (PTHrP) on calcium homeostasis in diabetes, we have measured the serum level and urinary excretion of PTHrP as well as other serum calcium-regulating hormones in 106 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 43 control subjects. The serum concentration of intact PTH was 2.34 +/- 0.13 (mean +/- SEM) pmol/l in NIDDM patients, which is significantly lower than the value of 3.11 +/- 0.14 pmol/l in the controls (p < 0.01). Both serum calcium and calcitonin, however, were not statistically different from controls. On the other hand, circulating PTHrP in NIDDM was 40.1 +/- 1.4 pmol/l, which is significantly elevated when compared to 27.3 +/- 1.3 pmol/l in the controls (p < 0.01). Moreover, urinary excretion of PTHrP also was significantly higher in NIDDM (p < 0.01). In the present study, the circulating calcium level was well preserved in NIDDM patients, although the PTH levels were shown to be decreased. The elevated serum PTHrP might, therefore, have a physiologically compensatory role on the calcium regulatory systems in NIDDM. Furthermore, this elevation is most likely due to the excess production of this peptide and not to the decrease in urinary excretion.
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PMID:Possible compensatory role of parathyroid hormone-related peptide on maintenance of calcium homeostasis in patients with non-insulin-dependent diabetes mellitus. 810 85

Hormonal control of skeletal growth, modeling, and remodeling is characterized by a complex interaction between the calciotropic hormones (25-hydroxycholecalciferol, 1,25-dihydroxycholecalciferol, parathyroid hormone, and calcitonin), growth, and thyroid hormones in addition to the estrogenic and androgenic gonadal hormones. Although both growth and thyroid hormones are essential skeletal growth and modeling and also can produce detrimental skeletal effects in adults when circulating in excess concentrations, these hormones assume a minor role in the day-to-day bone remodeling of the mature skeleton. Following the attainment of the peak bone mass, bone mineral content begins to decline in the fourth and fifth decades of life, accelerating in females in the first 5-7 years after the menopause as a result of estrogen deficiency. Associated with this age-dependent loss in skeletal mass are decreases in calcitonin reserve primarily in the 5-7 years following the menopause, decreases in circulating 25-hydroxycholecalciferol, intestinal resistance to 1,25-dihydroxycholecalciferol, and a gradual progressive rise in blood parathyroid hormone. These changes in calciotropic hormone profiles, together with poor nutritional habits, anticonvulsant, glucocorticoid, and thyroid medications, diseases such as type I diabetes, immobilization, or decreased physical activity all serve to weaken the aging skeleton. The result is a gradual and subtle change in skeletal anatomy, which progresses to alterations in vertebral structure, such as kyphosis, scoliosis, and pseudospondylolisthesis, and a variety of sciatic and nerve entrapment syndromes. Vertebral, forearm, and hip fractures and edentulism ultimately comprise the syndrome of age-related bone loss, resulting in lifestyle disabilities, extensive morbidity, analgesic drug abuse, hospitalization, and escalating annual health care expenditures.
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PMID:Hormonal alterations and osteoporotic syndromes. 812 20

CGRP (calcitonin gene-related peptide) is a potent vasodilator neuropeptide which acts on peri-arteriolar neurones and is implicated in the pathogenesis of numerous cardiovascular diseases. The synthesis of CGRP antagonists should be useful for the treatment of Raynaud's disease as well as migraine. There exists an homology between the structures of CGRP and pancreatic amylin and therefore an eventual role of CGRP in type II diabetes pathophysiology is currently being studied.
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PMID:[Calcitonin gene-related peptide (CGRP): a vasodilator neuropeptide with many potential applications]. 815 74

Glucocorticoids are highly valuable medication available to a physician, yet, their serious side effects have severely limited their use. Thus, the major purpose of our review is to provide a practical approach to increasing efficacy and minimizing side effects, that is increasing the benefit/risk ratio, of glucocorticoid therapy. The most effective way of avoiding their side effects, including infection, osteoporosis, atherosclerosis, is simply to avoid the overuse of glucocorticoids and to restrict their use to the truly indicated disease. Side effects can be reduced in part by the development of drug delivery systems, such as topical administration and targeting therapy. Combinations of calcium, vitamin D and sometimes thiazide or calcitonin, as compensatory therapy, have shown some favorable results for the prevention of osteoporosis. Although glucocorticoid therapy causes an increase of high-density lipoprotein and a decrease of lipoprotein (a) in serum, both are possibly preventive for atherosclerosis, hypertension and diabetes mellitus which are risk factors of atherosclerosis should be controlled. Future trends to remove their side effects will be obtained by more specific therapy based upon their pathogenesis.
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PMID:[Minimizing side effects of glucocorticoid therapy]. 816 80


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